Melanie S. Sanford

Bio: Melanie S. Sanford is an academic researcher from University of Michigan. The author has contributed to research in topics: Aryl & Palladium. The author has an hindex of 89, co-authored 287 publications receiving 31530 citations. Previous affiliations of Melanie S. Sanford include California Institute of Technology & Princeton University.

Palladium-Catalyzed Ligand-Directed C−H Functionalization Reactions

Abstract: 1.1 Introduction to Pd-catalyzed directed C–H functionalization The development of methods for the direct conversion of carbon–hydrogen bonds into carbon-oxygen, carbon-halogen, carbon-nitrogen, carbon-sulfur, and carbon-carbon bonds remains a critical challenge in organic chemistry. Mild and selective transformations of this type will undoubtedly find widespread application across the chemical field, including in the synthesis of pharmaceuticals, natural products, agrochemicals, polymers, and feedstock commodity chemicals. Traditional approaches for the formation of such functional groups rely on pre-functionalized starting materials for both reactivity and selectivity. However, the requirement for installing a functional group prior to the desired C–O, C–X, C–N, C–S, or C–C bond adds costly chemical steps to the overall construction of a molecule. As such, circumventing this issue will not only improve atom economy but also increase the overall efficiency of multi-step synthetic sequences. Direct C–H bond functionalization reactions are limited by two fundamental challenges: (i) the inert nature of most carbon-hydrogen bonds and (ii) the requirement to control site selectivity in molecules that contain diverse C–H groups. A multitude of studies have addressed the first challenge by demonstrating that transition metals can react with C–H bonds to produce C–M bonds in a process known as “C–H activation”.1 The resulting C–M bonds are far more reactive than their C–H counterparts, and in many cases they can be converted to new functional groups under mild conditions. The second major challenge is achieving selective functionalization of a single C–H bond within a complex molecule. While several different strategies have been employed to address this issue, the most common (and the subject of the current review) involves the use of substrates that contain coordinating ligands. These ligands (often termed “directing groups”) bind to the metal center and selectively deliver the catalyst to a proximal C–H bond. Many different transition metals, including Ru, Rh, Pt, and Pd, undergo stoichiometric ligand-directed C–H activation reactions (also known as cyclometalation).2,3 Furthermore, over the past 15 years, a variety of catalytic carbon-carbon bond-forming processes have been developed that involve cyclometalation as a key step.1b–d,4 The current review will focus specifically on ligand-directed C–H functionalization reactions catalyzed by palladium. Palladium complexes are particularly attractive catalysts for such transformations for several reasons. First, ligand-directed C–H functionalization at Pd centers can be used to install many different types of bonds, including carbon-oxygen, carbon-halogen, carbon-nitrogen, carbon-sulfur, and carbon-carbon linkages. Few other catalysts allow such diverse bond constructions,5,6,7 and this versatility is predominantly the result of two key features: (i) the compatibility of many PdII catalysts with oxidants and (ii) the ability to selectively functionalize cyclopalladated intermediates. Second, palladium participates in cyclometalation with a wide variety of directing groups, and, unlike many other transition metals, promotes C–H activation at both sp2 and sp3 C–H sites. Finally, the vast majority of Pd-catalyzed directed C–H functionalization reactions can be performed in the presence of ambient air and moisture, making them exceptionally practical for applications in organic synthesis. While several accounts have described recent advances, this is the first comprehensive review encompassing the large body of work in this field over the past 5 years (2004–2009). Both synthetic applications and mechanistic aspects of these transformations are discussed where appropriate, and the review is organized on the basis of the type of bond being formed.

Controlling Site Selectivity in Palladium-Catalyzed C–H Bond Functionalization

Abstract: Effective methodology to functionalize C–H bonds requires overcoming the key challenge of differentiating among the multitude of C–H bonds that are present in complex organic molecules. This Account focuses on our work over the past decade toward the development of site-selective Pd-catalyzed C–H functionalization reactions using the following approaches: substrate-based control over selectivity through the use of directing groups (approach 1), substrate control through the use of electronically activated substrates (approach 2), or catalyst-based control (approach 3). In our extensive exploration of the first approach, a number of selectivity trends have emerged for both sp2 and sp3 C–H functionalization reactions that hold true for a variety of transformations involving diverse directing groups. Functionalizations tend to occur at the less-hindered sp2 C–H bond ortho to a directing group, at primary sp3 C–H bonds that are β to a directing group, and, when multiple directing groups are present, at C–H si...

Mechanism and Activity of Ruthenium Olefin Metathesis Catalysts

Abstract: This report details the effects of ligand variation on the mechanism and activity of ruthenium-based olefin metathesis catalysts. A series of ruthenium complexes of the general formula L(PR3)(X)2RuCHR1 have been prepared, and the influence of the substituents L, X, R, and R1 on the rates of phosphine dissociation and initiation as well as overall activity for olefin metathesis reactions was examined. In all cases, initiation proceeds by dissociative substitution of a phosphine ligand (PR3) with an olefinic substrate. All of the ligands L, X, R, and R1 have a significant impact on initiation rates and on catalyst activity. The origins of the observed substituent effects as well as the implications of these studies for the design and implementation of new olefin metathesis catalysts and substrates are discussed in detail.

A Highly Selective Catalytic Method for the Oxidative Functionalization of C−H Bonds

Abstract: This communication describes a new and highly practical Pd(II)-catalyzed method for the regio- and chemoselective oxidative functionalization of arenes and alkanes. Carbon−hydrogen bonds of substrates that contain a variety of directing groups (e.g., pyridine, azobenzene, pyrazole, and imine derivatives) are selectively transformed into esters, ethers, and aryl-halides under mild conditions. The scope of this reaction in terms of substrate, directing group, and oxidant is described, and a preliminary catalytic cycle is proposed.

The Chemistry and Applications of Metal-Organic Frameworks

Abstract: Crystalline metal-organic frameworks (MOFs) are formed by reticular synthesis, which creates strong bonds between inorganic and organic units. Careful selection of MOF constituents can yield crystals of ultrahigh porosity and high thermal and chemical stability. These characteristics allow the interior of MOFs to be chemically altered for use in gas separation, gas storage, and catalysis, among other applications. The precision commonly exercised in their chemical modification and the ability to expand their metrics without changing the underlying topology have not been achieved with other solids. MOFs whose chemical composition and shape of building units can be multiply varied within a particular structure already exist and may lead to materials that offer a synergistic combination of properties.

Visible Light Photoredox Catalysis with Transition Metal Complexes: Applications in Organic Synthesis

Abstract: A fundamental aim in the field of catalysis is the development of new modes of small molecule activation. One approach toward the catalytic activation of organic molecules that has received much attention recently is visible light photoredox catalysis. In a general sense, this approach relies on the ability of metal complexes and organic dyes to engage in single-electron-transfer (SET) processes with organic substrates upon photoexcitation with visible light. Many of the most commonly employed visible light photocatalysts are polypyridyl complexes of ruthenium and iridium, and are typified by the complex tris(2,2′-bipyridine) ruthenium(II), or Ru(bpy)32+ (Figure 1). These complexes absorb light in the visible region of the electromagnetic spectrum to give stable, long-lived photoexcited states.1,2 The lifetime of the excited species is sufficiently long (1100 ns for Ru(bpy)32+) that it may engage in bimolecular electron-transfer reactions in competition with deactivation pathways.3 Although these species are poor single-electron oxidants and reductants in the ground state, excitation of an electron affords excited states that are very potent single-electron-transfer reagents. Importantly, the conversion of these bench stable, benign catalysts to redox-active species upon irradiation with simple household lightbulbs represents a remarkably chemoselective trigger to induce unique and valuable catalytic processes. Open in a separate window Figure 1 Ruthenium polypyridyl complexes: versatile visible light photocatalysts.

Density functionals with broad applicability in chemistry.

Abstract: Although density functional theory is widely used in the computational chemistry community, the most popular density functional, B3LYP, has some serious shortcomings: (i) it is better for main-group chemistry than for transition metals; (ii) it systematically underestimates reaction barrier heights; (iii) it is inaccurate for interactions dominated by medium-range correlation energy, such as van der Waals attraction, aromatic−aromatic stacking, and alkane isomerization energies. We have developed a variety of databases for testing and designing new density functionals. We used these data to design new density functionals, called M06-class (and, earlier, M05-class) functionals, for which we enforced some fundamental exact constraints such as the uniform-electron-gas limit and the absence of self-correlation energy. Our M06-class functionals depend on spin-up and spin-down electron densities (i.e., spin densities), spin density gradients, spin kinetic energy densities, and, for nonlocal (also called hybrid)...

Palladium-Catalyzed Ligand-Directed C−H Functionalization Reactions

Abstract: 1.1 Introduction to Pd-catalyzed directed C–H functionalization The development of methods for the direct conversion of carbon–hydrogen bonds into carbon-oxygen, carbon-halogen, carbon-nitrogen, carbon-sulfur, and carbon-carbon bonds remains a critical challenge in organic chemistry. Mild and selective transformations of this type will undoubtedly find widespread application across the chemical field, including in the synthesis of pharmaceuticals, natural products, agrochemicals, polymers, and feedstock commodity chemicals. Traditional approaches for the formation of such functional groups rely on pre-functionalized starting materials for both reactivity and selectivity. However, the requirement for installing a functional group prior to the desired C–O, C–X, C–N, C–S, or C–C bond adds costly chemical steps to the overall construction of a molecule. As such, circumventing this issue will not only improve atom economy but also increase the overall efficiency of multi-step synthetic sequences. Direct C–H bond functionalization reactions are limited by two fundamental challenges: (i) the inert nature of most carbon-hydrogen bonds and (ii) the requirement to control site selectivity in molecules that contain diverse C–H groups. A multitude of studies have addressed the first challenge by demonstrating that transition metals can react with C–H bonds to produce C–M bonds in a process known as “C–H activation”.1 The resulting C–M bonds are far more reactive than their C–H counterparts, and in many cases they can be converted to new functional groups under mild conditions. The second major challenge is achieving selective functionalization of a single C–H bond within a complex molecule. While several different strategies have been employed to address this issue, the most common (and the subject of the current review) involves the use of substrates that contain coordinating ligands. These ligands (often termed “directing groups”) bind to the metal center and selectively deliver the catalyst to a proximal C–H bond. Many different transition metals, including Ru, Rh, Pt, and Pd, undergo stoichiometric ligand-directed C–H activation reactions (also known as cyclometalation).2,3 Furthermore, over the past 15 years, a variety of catalytic carbon-carbon bond-forming processes have been developed that involve cyclometalation as a key step.1b–d,4 The current review will focus specifically on ligand-directed C–H functionalization reactions catalyzed by palladium. Palladium complexes are particularly attractive catalysts for such transformations for several reasons. First, ligand-directed C–H functionalization at Pd centers can be used to install many different types of bonds, including carbon-oxygen, carbon-halogen, carbon-nitrogen, carbon-sulfur, and carbon-carbon linkages. Few other catalysts allow such diverse bond constructions,5,6,7 and this versatility is predominantly the result of two key features: (i) the compatibility of many PdII catalysts with oxidants and (ii) the ability to selectively functionalize cyclopalladated intermediates. Second, palladium participates in cyclometalation with a wide variety of directing groups, and, unlike many other transition metals, promotes C–H activation at both sp2 and sp3 C–H sites. Finally, the vast majority of Pd-catalyzed directed C–H functionalization reactions can be performed in the presence of ambient air and moisture, making them exceptionally practical for applications in organic synthesis. While several accounts have described recent advances, this is the first comprehensive review encompassing the large body of work in this field over the past 5 years (2004–2009). Both synthetic applications and mechanistic aspects of these transformations are discussed where appropriate, and the review is organized on the basis of the type of bond being formed.

Autonomic healing of polymer composites

Abstract: Structural polymers are susceptible to damage in the form of cracks, which form deep within the structure where detection is difficult and repair is almost impossible. Cracking leads to mechanical degradation of fibre-reinforced polymer composites; in microelectronic polymeric components it can also lead to electrical failure. Microcracking induced by thermal and mechanical fatigue is also a long-standing problem in polymer adhesives. Regardless of the application, once cracks have formed within polymeric materials, the integrity of the structure is significantly compromised. Experiments exploring the concept of self-repair have been previously reported, but the only successful crack-healing methods that have been reported so far require some form of manual intervention. Here we report a structural polymeric material with the ability to autonomically heal cracks. The material incorporates a microencapsulated healing agent that is released upon crack intrusion. Polymerization of the healing agent is then triggered by contact with an embedded catalyst, bonding the crack faces. Our fracture experiments yield as much as 75% recovery in toughness, and we expect that our approach will be applicable to other brittle materials systems (including ceramics and glasses).